Estradiol Decreases Xanthine Dehydrogenase Enzyme Activity and Protein Expression in Non-Tumorigenic and Malignant Human Mammary Epithelial Cells

The retinoic acid deficiency in breast tumour epithelial cells has been ascribed to an insufficient expression of either the enzyme(s) involved in its biosynthesis or the cellular retinol binding protein (CRBP) or both. In an attempt to define the mechanisms underpinning retinoic acid deficiency in these cell model systems, we have investigated the potential regulatory effect of oestrogen (17b-estradiol) on one key player in retinoic acid biosynthesis, the xanthine dehydrogenase (XDH). This enzyme is consistently expressed and very active in non-malignant human mammary epithelial cells (HMEC), as opposed to tumour MDA-MB231 and MCF7 cells. In these latter two cell lines, as opposed to HMEC cells, we observe a residual ability of XDH to produce retinoic acid from retinaldehyde and the inability to use retinol, as a consequence of a deficit in CRBP. In addition, estradiol treatment of MDA-MB231 and MCF7 cells decreases protein expression and activity of the enzyme, with no modification of the mRNA transcript levels, eventually leading to deteriorate further retinoic acid production